The proposed research is aimed at resolving the observed differences and the greater variability of detoxification mechanisms between the fetus, neonate and the adult. We have isolated and prepared monospecific antibodies to several individual forms of cytochrome P-450, a major enzyme of drug metabolism. Employing these antibodies and standard electrophoretic techniques, we have identified two separate forms of hepatic microsomal cytochrome P-448 from rabbits which are differentially induced in the neonatal as compared to the adult period. We are now planning to record the time of appearance and of inducibility of the individual forms of cytochrome P-450 in the developing organism. Our aim is to examine which factors regulate the temporal occurrence and induction of cytochrome P-450. The properties of each of the forms of cytochrome P-450 will be studied as they relate to their function, assembly, and metabolism. With a radioimmunoassay developed with the monospecific antibodies, we will be able to quantitate each cytochrome in tissues of fetuses, neonates, growing and adult animals. By an immunohistochemical, light-microscopic technique we plan to demonstrate at which time during development a given form appears and which tissues and cell types contain those forms. It is expected that the basic (Macromolecular) information examined in an animal system will provide the much needed information for the development of rational preventive and therapeutic regimens for protection of the unborn and new-born child.